The primary aims of the NMR core are to provide infrastructure and support for structural analysis of target macromolecules, their mutual interactions and with candidate drug molecules obtained from in silico searches and optimization and metabolomics of cancer cells and tissue. This includes stable isotope labeling strategies including N-15 and C-13 precursors. Our goals continue to be to streamline both data collection and analysis as well as introduce new labeling strategies to provide more detailed information about specific metabolic pathways, via Stable Isotope Resolved Metabolomics (SIRM). This includes NMR structural and biophysical analysis of macromolecules and their interactions with small molecules, as well as extensive use of the metabolomics capabilities of the Core as a part of the drug discovery/development process. A large fraction of research projects that use the facility are translational, using purified components, as well as animal models and human subjects. The NMR-based studies operate in tandem with activates of other Cores, especially the Modeling Core and, in the future, with the Transgenic Mouse Core. NMR is one of the few techniques that provides localized imaging and high resolution, high information content spectroscopy in vivo. This will be a major new direction of the Core. The overall goals of the Core will be achieved via the following Specific Aims: 1. Provide NMR instrumentation and expertise for characterizing macromolecules and their interactions; 2. Provide the instrumentation and expertise for metabolomics studies; 3. Facilitate structure-based drug design for drug discovery and drug development; 4. Develop and implement new experiments and capabilities including stable isotope resolved metabolomics on small animals, in vivo; 5. Educate members of the community on the specific capabilities of NMR for their research projects; 6. Provide training of students and fellows in cancer biochemistry and drug development. These Aims complement those of the other Cores in terms of the overall research mission of the Cancer Center and the University.